•6-Gingerol attenuates pyroptosis in septic mice.•6-Gingerol inhibits macrophage pyroptosis and release of inflammatory cytokines.•6-Gingerol attenuates macrophage pyroptosis by blocking MAPK ...activation.•ERK agonist produced the opposite effects.
Sepsis is a major cause of death for ICU patients. Sepsis development depends heavily on the presence of mature IL-1β cytokine. This study evaluates the potential therapeutic properties of a bioactive compound known as 6-gingerol on sepsis. This compound has previously been demonstrated to possess anti-inflammatory properties both in vivo and in vitro.
C57BL/6 mice was used to establish models of sepsis by means of cecal ligation and puncture (CLP). Upon treatment with 6-gingerol, we assessed the survival rate of mice and measured the levels of key pro-inflammatory cytokines in serum and colon tissues. Sepsis pathogenesis was further explored using the RAW264.7 cell line and bone marrow-derived macrophages (BMDMs) treated with ATP and lipopolysaccharide (LPS). The impact of 6-gingerol on pyroptosis was also examined. In addition, we assessed the role of MAPK signaling in 6-gingerol-induced effects in BMDMs and RAW264.7 cells.
In CLP mice, 6-gingerol significantly ameliorated sepsis development, which was associated with the reduction of serum IL-1β. In BMDMs and RAW264.7 cells, 6-gingerol strongly attenuated pyroptosis as well as the release of caspase-1p20, HMGB1, mature IL-1β, IL-18 in response to ATP and LPS treatment. 6-Gingerol conferred these effects by blocking MAPK activation. Exposure to an ERK agonist (EGF) reversed effects of 6-gingerol, causing pyroptosis, LDH and caspase-1p20 release.
By targeting MAPK signaling, 6-gingerol significantly suppressed secretion of pro-inflammatory cytokines and inhibited macrophage cells pyroptosis resulting in overall inhibition of sepsis development.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Two indexes, latent heat accumulated temperature value (LHATV) and latent heat thermoregulation index (LHTI) were proposed for evaluating the temperature regulation effect of micro-PCMs.•Outdoor ...cube models buried in sufficient temperature sensors to monitor the temperature changes in real time were adopted.•The latent heat thermoregulation of micro-PCMs was mainly affected by time and temperature domain.
Phase change materials (PCMs) can effectively adjust the temperature of asphalt pavement and have broad application prospects. Microencapsulated phase change materials (micro-PCMs) can solve the leaking problem of PCMs, which easily occurs during the heating process of the asphalt mineral mixture. This paper is intended to provide two indices to evaluate the temperature regulation effect of micro-PCMs: the latent heat accumulated temperature value (LHATV) and latent heat thermoregulation index (LHTI). The LHATV reflects the thermal regulation capability of micro-PCMs and the accumulation in temperature difference in a certain time range. The LHTI represents the completion degree of latent heat in unit time and unit temperature, and it reflects the efficiency of latent heat thermoregulation. The outdoor cube model test was conducted on two cube models with dimensions of 30 cm × 30 cm × 30 cm. Each cube model consisted of three asphalt specimens with dimensions of 30 cm × 30 cm × 10 cm. The first cube model, which was mixed with 0.3% wt of micro-PCMs, served as the experimental group, and the other cube model without micro-PCMs addition served as the control group. Inside the two cube models, sufficient temperature sensors were placed to monitor the temperature. The analysis results show that there is a transformable relationship between the latent heat time domain and the temperature domain. In the moderate temperature range and time span, the latent heat thermal stabilization of micro-PCMs can be efficient.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To evaluate the influence of age and axial length (AL) on the position of the fovea in patients with high myopia (HM).
In this prospective study, 96 patients (186 eyes) with HM were consecutively ...recruited from the Third Affiliated Hospital of Nanchang University. DRI-OCT Atlantis, fundus imaging, and IOL Master were used in this study. Three indices were measured: the distance between the fovea and the optic nerve head (ONH) center (DFO), the vertical distance between the fovea and the horizontal line pass of the ONH center (VDFO), and the horizontal distance between the fovea and the vertical line pass of the ONH center (HDFO). These measurements were used to analyze the effects of different age groups (A1, A2, A3 groups) and AL (AL1, AL2, AL3, AL4 groups) on these indices.
The results showed that there was no statistical significance in DFO among the age and AL groups (
=0.46, 0.37;
=0.62, 0.76, respectively). In HDFO, there was also no statistical significance among the age and AL groups (
=0.10, 0.48;
=0.90, 0.69, respectively). In VDFO, however, the difference in the age and AL groups was statistically significant (
=3.21, 3.12;
=0.04, 0.02, respectively). Thus, VDFO were correlated with age and AL (
=0.21, 0.23, all
<0.01), while HDFO and DFO were not correlated with age and AL (
=0.30,
>0.05).
In high myopia, the foveal position changes mainly in the vertical direction along with factors of age and AL.
•The microencapsulation can solve the leakage of PCM in high temperature.•The specimen with temperature sensors was developed to give temperature recording.•Two indices, LHATV and LHTI were ...established to evaluate the latent heat effect.•The thermoregulation effect was mainly affected by time and temperature domain.•The solar radiation and air flow are the important factors affecting the Micro-PCM.•The thermoregulation can be exerted under medium temperature and time span.
To analyze the latent heat thermoregulation effect of the microencapsulated phase change material (Micro-PCM) on the pavement asphalt mixture, 300 mm × 300 mm × 300 mm outdoor cubic specimen made up of asphalt mixture with the Micro-PCM was prepared. By arranging a sufficient number of temperature sensors inside the specimen, a real-time monitoring system was established to record the temperature variations of the specimen. Two indices, the latent heat accumulated temperature value (LHATV) and latent heat thermoregulation index (LHTI) were proposed to evaluate the latent heat thermoregulation performance of the Micro-PCM under heating and cooling processes. The results showed that the solar radiation and air flow conditions were the important factors affecting the latent heat effect of the Micro-PCM. The responses of the heat transfer process of the Micro-PCM varied at different locations inside the specimen, which caused a difference in the latent heat efficiency. Meanwhile, under the conditions where the ambient temperature changed rapidly, the phase change response inside the specimen would be relatively lagged, the process of latent heat storage was hindered, and the heat couldn’t be completely converted to the latent form. It can be conclude that the excessive heating and cooling rates will affect the process of latent heat, the thermoregulation efficiency of the Micro-PCM can be maintained at a high level under the appropriate variable temperature conditions, a medium temperature range and time span. Under these conditions, the Micro-PCM can exert an effective latent heat thermoregulation function to asphalt mixture.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Liver metastasis is a leading indicator of poor prognosis in patients with colorectal cancer (CRC). Exosomal intercellular communication has been reported to play an important role in cancer invasion ...and metastasis. Here, we characterized exosomal miRNAs underlying liver metastasis in CRC patients (Cohort 1, n = 30) using miRNA arrays. Exosomal miR-150 was found to be downregulated in CRC patients with liver metastases compared to those without (P = 0.025, fold change FC = 2.01). These results were then validated using another independent cohort of CRC patients (Cohort 2, n = 64). Patients with low expression of exosomal miR-150 had significantly shorter overall survival (OS) time (33.3 months versus 43.3 months, P = 0.002). In addition, the low expression of exosomal miR-150 was significantly correlated with advanced tumor node metastasis staging (P = 0.013), higher CA199 level (P = 0.018), and the presence of liver metastasis (P = 0.048). Multivariate analysis showed that low expression of exosomal miR-150 (P = 0.035) and liver metastasis (P < 0.001) were independent prognostic factors for overall survival. In vivo and in vitro studies showed that the viability and invasion of CRC cells were both significantly suppressed by ExomiR-150. Target-prediction assessment and dual-luciferase reporter assay indicated that FTO (the fat mass and obesity-associated gene) was a direct target for miR-150. This study first demonstrated that exosomal miR-150 may be a potential prognostic factor and treatment target for CRC.
To clarify the gel formation mechanism of isolated proteins recovered from blue round scads by isoelectric solubilization/precipitation, the physiochemical, conformational and gelation properties of ...the major protein myosin treated by acidic-(AM) or alkaline-(KM) pH-shifting were investigated and compared with native myosin (NM). The solubility in all myosin samples dropped significantly at 40 °C, with remarkable increases of particle size, turbidity and surface hydrophobicity. Among the samples, AM exhibited the lowest solubility and highest turbidity than NM and KM as the temperature was higher than 40 °C, indicating that AM is easily to be denatured and aggregated. Circular dichroism (CD) analysis showed that both acidic and alkaline pH treatments led to conformational changes of myosin, together with α-helix content variations. When pH was readjusted to neutral, KM recovered its structure similar to NM, while AM failed to refold to its native state. NM exhibited the highest storage modulus (G′) at 90 °C, while AM revealed the lowest G′ value. Furthermore, AM did not change obviously during heating, especially at the gelling temperature range (60–90 °C). These results strongly suggested that acidic treatment led to an irreversible conformational change in myosin, consequently induced a fierce denaturation and aggregation at the initial stage of heating, and eventually led to a complete loss of gel-forming ability. Alkaline pH-shifting, on the other hand is thus more feasible for protein recovery from blue round scads.
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•Myosin was isolated from blue round scads and treated by acidic or alkaline pH-shifting.•Acidic pH-shifting caused irreversible conformational change in myosin and the loss of its gel-forming ability.•Alkaline pH-shifting is more feasible for protein recovery from blue round scads.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Oliguria is often viewed as a sign of renal hypoperfusion and an indicator for volume expansion during surgery. However, the prognostic association and the predictive utility of intraoperative ...oliguria for postoperative acute kidney injury (AKI) are unclear.
We conducted a retrospective cohort study on patients undergoing major thoracic surgery in an academic hospital to assess the association of intraoperative oliguria with postoperative AKI and its predictive value. To contextualise our findings, we included our results in a meta-analysis of observational studies on the importance of oliguria during noncardiac surgery.
In our cohort study, 3862 patients were included; 205 (5.3%) developed AKI after surgery. Intraoperative urine output of 0.3 ml kg−1 h−1 was the optimal threshold for oliguria in multivariable analysis. Patients with oliguria had an increased risk of AKI (adjusted odds ratio: 2.60; 95% confidence interval: 1.24–5.05). However, intraoperative oliguria had a sensitivity of 5.9%, specificity of 98%, positive likelihood ratio of 2.74, and negative likelihood ratio of 0.96, suggesting poor predictive ability. Moreover, it did not improve upon the predictive performance of a multivariable model, based on discrimination and reclassification indices. Our findings were generally consistent with the results of a systematic review and meta-analysis, including six additional studies.
Intraoperative oliguria has moderate association with, but poor predictive ability for, postoperative AKI. It remains of clinical interest as a risk factor potentially modifiable to interventions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Postoperative atrial fibrillation/flutter (POAF) is associated with significant morbidity and mortality after general thoracic surgery, but the need for and the best agent for prophylaxis remains ...obscure.
A systematic literature search was performed to identify randomized controlled trials that compared regimens for POAF prophylaxis after general thoracic surgery. Random-effects meta-analyses with trial sequential analyses were performed to compare the effects of medical prophylaxis vs placebo/usual care. The risk of POAF among patients receiving various prophylactic regimens was subjected to Bayesian network meta-analysis.
Twenty-two trials (2,891 patients and 11 regimens) were included. Overall, medical prophylaxis reduced the incidence of POAF (OR, 0.33; 95% CI, 0.22-0.49) but not short-term mortality (OR, 0.85; 95% CI, 0.41-1.73). There was no significant difference in patient withdrawal due to adverse events (OR, 1.67; 95% CI, 0.67-4.16). Trial sequential analysis showed that as of 2012, sufficient evidence had accrued in support of the effectiveness of medical prophylaxis in reducing POAF after general thoracic surgery. In network meta-analysis, β-blockers, angiotensin-converting enzyme inhibitors, amiodarone, magnesium, and calcium channel blockers significantly reduced the risk of POAF compared with placebo/usual care. β-Blockers had the highest probability of being the most effective agents (OR, 0.12; 95% credible interval CrI, 0.05-0.27; probability of being best, 77.7%; number needed to treat, 5.2).
The current literature supports the effectiveness and tolerability of medical prophylaxis and the superiority of β-blockers in preventing POAF after general thoracic surgery. β-Blockers are recommended, taking into consideration the status of the bronchopulmonary system.
Introduction. The systematic meta-analysis of randomized controlled trials (RCTs) evaluated the effects of intraoperative ulinastatin on early-postoperative recovery in patients undergoing cardiac ...surgery. Methods. RCTs comparing intraoperative ulinastatin with placebo in cardiac surgery were searched through PubMed, Cochrane databases, Medline, SinoMed, and the China National Knowledge Infrastructure (1966 to May 20th, 2013). The primary endpoints included hospital mortality, postoperative complication rate, length of stay in intensive care unit, and extubation time. The physiological and biochemical parameters illustrating postoperative cardiac and pulmonary function as well as inflammation response were considered as secondary endpoints. Results. Fifteen RCTs (509 patients) met the inclusion criteria. Ulinastatin did not affect hospital mortality, postoperative complication rate, or ICU length of stay but reduced extubation time. Ulinastatin also increased the oxygenation index on postoperative day 1 and reduced the plasma level of cardiac troponin-I. Additionally, ulinastatin inhibited the increased level of tumor necrosis factor-alpha, polymorphonuclear neutrophil elastase, interleukin-6, and interleukin-8 associated with cardiac surgery. Conclusion. Ulinastatin may be of value for the inhibition of postoperative increased inflammatory agents and most likely provided pulmonary protective effects in cardiac surgery. However, larger adequately powered RCTs are required to define the clinical effect of ulinastatin on postoperative outcomes in cardiac surgery.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Objectives
Chitinase 3-like 1 (CHI3L1) is associated with poor prognosis of various human cancers. However, the clinical and prognostic significance of CHI3L1 in hepatocellular carcinoma (HCC) is ...largely unknown. The aim of the present study is to investigate the expression of CHI3L1 in human HCC cell lines, clinical HCC specimens and its association with expressions of phosphorylated-Akt (p-Akt), E-cadherin and prognostic significance.
Methods
The protein level of CHI3L1 in HCC cell lines was evaluated by western blot. The mRNA and protein levels of CHI3L1 in 19 self-paired HCC specimens were assessed by RT-PCR and western blot assays. The clinical and prognostic significance of CHI3L1 in 70 cases of HCC patients was determined by immunohistochemistry. In addition, expressions of p-Akt and E-cadherin were also assessed.
Results
The protein level of CHI3L1 paralleled with increased malignant potential of HCC cell lines (
P
< 0.05). The mRNA and protein levels of CHI3L1 in HCC tissues were up-regulated compared with those in adjacent peritumoral tissues and further increased in tumors with metastasis (
P
< 0.05). Clinicopathological analysis showed that positive CHI3L1 expression was significantly associated with larger tumor size, capsular invasion, advanced TNM stages and status of metastasis (
P
= 0.035, 0.003, 0.023 and 0.003, respectively). Furthermore, CHI3L1 expression was positively correlated with high level of p-Akt (
r
= 0.293,
P
= 0.014), but inversely correlated with expression of E-cadherin (
r
= −0.267,
P
= 0.026). Additionally, Kaplan–Meier survival analysis showed that HCC patients with positive CHI3L1 expression had a worse overall survival and disease-free survival compared with those with negative CHI3L1 expression (
P
< 0.001, respectively). Multivariate analysis identified CHI3L1 as an independent prognostic predictor for overall survival and disease-free survival of HCC patients (
P
= 0.044 and 0.031, respectively).
Conclusions
CHI3L1 plays an essential role in HCC malignancies and may be served as a valuable prognostic biomarker for HCC patients.
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EMUNI, NUK, SBMB, SBNM, UL, UPUK